Synthesis and characterization of a chitosan-N-acetyl cysteine conjugate

Schmitz, Thierry; Grabovac, Vjera; Palmberger, Thomas F.; Hoffer, Martin; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2007.06.040

Cited by 107 publications

(65 citation statements)

References 26 publications

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“…[94] These polymers can be prepared by conjugating conventional mucoadhesive polymers with molecules carrying thiol functionality. Typical examples of polymeric thiomers include the following conjugates: poly(acrylic acid)/cystein, [95] chitosan/N-acetylcystein, [96] alginate/cystein, [97] chitosan/thioglycolic acid [98] and chitosan/thioethylamidine. [99] The mucoadhesive properties of polymeric thiomers have been extensively studied by Bernkop-Schnurch and coworkers.…”

Section: Polymeric Thiomersmentioning

confidence: 99%

Advances in Mucoadhesion and Mucoadhesive Polymers

Khutoryanskiy

2010

Macromolecular Bioscience

530

421

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Mucoadhesion is the ability of materials to adhere to mucosal membranes in the human body and provide a temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal drug delivery. Excellent mucoadhesive properties are typical for hydrophilic polymers possessing charged groups and/or non-ionic functional groups capable of forming hydrogen bonds with mucosal surfaces. This feature article considers recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview on the structure of mucosal membranes, properties of mucus gels and the nature of mucoadhesion. It describes the most common methods to evaluate mucoadhesive properties of various dosage forms and discusses the main classes of mucoadhesives.

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Section: Polymeric Thiomersmentioning

confidence: 99%

Advances in Mucoadhesion and Mucoadhesive Polymers

Khutoryanskiy

2010

Macromolecular Bioscience

530

421

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“…Chitosan-based nanoparticles were added to PLGA microparticles using the w/o/w double emulsion method (36) , with modifications. Briefly, 100 mg of PLGA was dissolved in 2.5 mL of DCM.…”

Section: Preparation Of a System-within-system Composed Of Chitosan-mentioning

confidence: 99%

“…This effect may also contribute to the absence of an initial burst release and slower release compared to all of the other preparations (Section 3.5). Finally, CNAC is more viscous than chitosan (36) and studies have shown that increasing the viscosity of the PLGA matrix improves protein loading (75) . …”

Section: Particle Morphology Assessed Using Semmentioning

confidence: 99%

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

et al. 2016

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Age-related macular degeneration (AMD) is the leading cause of certified vision loss worldwide. The standard treatment for neovascular AMD involves repeated intravitreal injections of therapeutic proteins directed against vascular endothelial growth factor, such as ranibizumab. Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), form delivery vehicles which can be used to treat posterior segment eye diseases, but suffer from poor protein loading and release. This work describes a 'system-within-system', PLGA microparticles incorporating chitosan-based nanoparticles, for improved loading and sustained intravitreal delivery of ranibizumab. Chitosan-N-acetyl-L-cysteine (CNAC) was synthesized and its synthesis confirmed using FT-IR and 1 H NMR. Chitosan-based nanoparticles comprised of CNAC, CNAC/tripolyphosphate (CNAC/TPP), chitosan, chitosan/TPP (chit/TPP) or chit/TPP-hyaluronic acid (chit/TPP-HA) were incorporated in PLGA microparticles using a modified w/o/w double emulsion method. Nanoparticles and final nanoparticles-within-microparticles were characterized for their protein-nanoparticle interaction, size, zeta potential, morphology, protein loading, stability, in vitro release, in vivo anti-angiogenic activity and effects on cell viability. The prepared nanoparticles were 17 -350 nm in size and had zeta potentials of -1.4 to +12 mV. Microscopic imaging revealed spherical nanoparticles on the surface of PLGA microparticles for preparations containing chit/TPP, CNAC and CNAC/TPP. Ranibizumab entrapment efficiency in the preparations varied between 13 -69% and was highest for the PLGA microparticles containing CNAC nanoparticles. This preparation also showed the slowest release with no initial burst release compared to all other preparations. Incorporation of TPP to this formulation increased the rate of protein release and reduced entrapment efficiency. PLGA microparticles containing chit/TPP-HA showed the fastest and near-complete release of ranibizumab. All of the prepared empty particles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Ranibizumab released from all preparations maintained its structural integrity and in vitro activity. The chit/TPP-HA preparation enhanced anti-angiogenic activity and may provide a potential biocompatible platform for enhanced anti-angiogenic activity in combination with ranibizumab. In conclusion, the PLGA microparticles containing CNAC nanoparticles, showed significantly improved ranibizumab loading and release profile. This novel drug delivery system may have potential for improved intravitreal delivery of therapeutic proteins, thereby reducing the frequency, risk and cost of burdensome intravitreal injections.

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“…In contrast, at pH above 5 the yield of xyloglucan bonded thiol groups decreased again. A reason for this observation can be seen in the oxidation of the sulfhydryl groups during the coupling reaction which is favored at higher pH-values (Schmitz et al, 2008) and increased share of disulfide bond formation between two thiol groups. The differences were found to be significant after a multiple comparison test followed by Tucky test (p<0.05) using PRIMER software.…”

Section: Thiol and Disulphide Group Contentmentioning

confidence: 99%

Synthesis and characterization of a cysteine xyloglucan conjugate as mucoadhesive polymer

Bhalekar¹,

Sonawane

Shimpi³

2013

Braz. J. Pharm. Sci.

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The aim of this study was to improve the mucoadhesive potential of xyloglucan polymer by the covalent attachment of cysteine as thiol moiety. The parent polymer xyloglucan was chemically modified by introducing sulphydryl bearing compound L-cysteine HCl. Different batches of xyloglucan-cysteine conjugates were prepared at varying reaction pH (2-6) and evaluated for optimum thiol incorporation, disulphide group content, swelling behavior, rheological properties and mucoadhesive properties. The obtained conjugates characterized in vitro by quantification of immobilized thiol groups; showed maximum thiol incorporation on xyloglucan (7.67 ± 0.14 %) at pH 5. The disulphide group content was found maximum (2.83 ± 0.12) at pH 6. The water uptake at end of 4 h was 5.0 for xyloglucan and was found to decrease in thiolated derivatives with increase in thiolation. Mucoadhesion studies revealed that mucoadhesion of xyloglucan-cysteine conjugate increased more than twice compared to the unmodified polymer. The viscosity of thiomer was more than that of xyloglucan because of formation of disulphide bonds.Uniterms: Mucoadhesion. Thiomer. Xyloglucan. L-cysteine HCl.O objetivo deste estudo foi melhorar o potencial mucoadesivo do polímero xiloglicano pela ligação covalente de cisteína como unidade de tiol. O polímero xiloglicano foi quimicamente modificado pela introdução de cloridrato de cisteína como grupo contendo sulfidrila. Prepararam-se diferentes lotes de conjugados cisteína-xiloglicano em pH variando de 2 a 6, avaliando-se a incorporação ótima de tiol, o conteúdo de dissulfeto, o comportamento de inchamento, as propriedades reológicas e mucoadesivas. Os conjugados obtidos foram caracterizados in vitro pela quantificação de grupos tiol, mostrando máxima incorporação na xiloglicana (7.67 ± 0.14 %) em pH 5. O conteúdo de grupos dissulfeto foi máximo (2.83 ± 0.12) em pH 6. O índice de inchamento em % no fim de 4 h foi 83.87 para o xiloglicano e diminuiu para os derivados tiolados. O conteúdo foi mínimo para TH2 (78.26), aumentou pouco até TH5 (83.33) e diminuiu, posteriormente, para TH6 (80.13). Os estudos de mucoadesão revelaram que o conjugado xiloglicano-cisteína aumentou mais que duas vezes comparativamente ao polímero não modificado. A viscosidade do tiômero foi maior do que a do xiloglicano devido à formação das ligações dissulfeto.

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Synthesis and characterization of a chitosan-N-acetyl cysteine conjugate

Cited by 107 publications

References 26 publications

Advances in Mucoadhesion and Mucoadhesive Polymers

Advances in Mucoadhesion and Mucoadhesive Polymers

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

Synthesis and characterization of a cysteine xyloglucan conjugate as mucoadhesive polymer

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